Long-term outcomes in medullary thyroid cancer patients treated with [¹⁷⁷Lu]Lu-DOTAGA.FAPi dimer therapy

Fibroblast activation protein (FAP)-targeted radionuclide therapy is a promising approach for patients with advanced or metastatic medullary thyroid carcinoma (MTC). This study evaluates efficacy, safety, and survival outcomes of [¹⁷⁷Lu]/[²²⁵Ac]-DOTAGA.Glu.(FAPi)₂ therapy in this population.

Nineteen patients with progressive MTC were treated with either [¹⁷⁷Lu]Lu-DOTAGA.Glu.(FAPi)₂ or [²²⁵Ac]Ac-DOTAGA.Glu.(FAPi)₂, receiving a median of 5 cycles. The median cumulative activity administered was 20.3 GBq (Lu) and 6.66 MBq (Ac) and the median follow-up was 21 months. Of the 17 evaluable patients, radiological response was assessed in 15 patients using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). The analysis demonstrated a partial response (PR) in 33% of patients, stable disease (SD) in 47%, and progressive disease (PD) in 20%, resulting in a disease control rate (DCR) of 80%. Positron emission tomography response criteria in solid tumors (PERCIST) evaluation (n = 15) showed 47% PR, 40% SD, and 13% PD. Biochemical response was evaluable in 14 patients: 64.2% showed stable or decreasing tumor markers. Median calcitonin doubling time was 6.7 months. Clinical progression occurred in 2 patients. Median PFS was 26 months; median OS was 42 months. No statistically significant difference in OS was observed between progression and non-progression groups (log-rank p-0.758). No Grade 4 or life-threatening toxicities were observed. Only two patients experienced Grade 3 adverse events-one with elevated alkaline phosphatase and one with worsening anemia. All other hematologic and biochemical toxicities were limited to Grade 1-2.

[¹⁷⁷Lu]/[²²⁵Ac]-DOTAGA.Glu.(FAPi)₂ therapy shows encouraging disease control, acceptable safety, and preliminary efficacy signals such as increased survival in the treated patients of advanced MTC.